Journal
BIOMACROMOLECULES
Volume 22, Issue 10, Pages 4383-4394Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.1c00960
Keywords
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Funding
- National Natural Science Foundation of China [51725303, 52033007]
- Fundamental Research Funds for the Central Universities [2682019CX76]
- Sichuan Science and Technology Program [2020YFH0052]
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This study developed a pH-sensitive polymeric vesicle for co-delivery of GOx and BSO, which can induce starvation therapy in cancer cells by consuming glucose and activating the ferroptosis signaling pathway. In vivo results showed that GOx/BSO@CS PVs effectively inhibited the growth of 4T1 tumors in mice, indicating a promising strategy for synergistic starvation-ferroptosis therapy in tumor treatment.
Typical glucose oxidase (GOx)-based starvation therapy is a promising strategy for tumor treatment; however, it is still difficult to achieve an effective therapeutic effect via a single starvation therapy. Herein, we designed a pH-sensitive polymeric vesicle (PV) self-assembled by histamine-modified chondroitin sulfate (CS-his) for codelivery of GOx and L-buthionine sulfoximine (BSO). GOx can consume glucose to induce the starvation therapy after the PVs reach cancer cell. Moreover, the product H2O2 will be reduced by a high concentration of glutathione (GSH) in the tumor cell, resulting in a reduction of the GSH content. The released BSO finally further reduced the GSH level. As a result, the signaling pathway of the ferroptosis will be activated. The in vivo results demonstrated that GOx/BSO@CS PVs exhibit a good inhibitory effect on the growth of 4T1 tumors in mice. Thus, this work provides a facile strategy to prepare pH-sensitive nanomedicine for synergistic starvation-ferroptosis therapy of tumor.
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